Prevalence of pathogenic/likely pathogenic variants in the 24 cancer genes of the ACMG Secondary Findings v2.0 list in a large cancer cohort and ethnicity-matched controls.
Genome Med
; 10(1): 99, 2018 12 24.
Article
em En
| MEDLINE
| ID: mdl-30583724
ABSTRACT
BACKGROUND:
Prior research has established that the prevalence of pathogenic/likely pathogenic (P/LP) variants across all of the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes is approximately 0.8-5%. We investigated the prevalence of P/LP variants in the 24 ACMG SF v2.0 cancer genes in a family-based cancer research cohort (n = 1173) and in cancer-free ethnicity-matched controls (n = 982).METHODS:
We used InterVar to classify variants and subsequently conducted a manual review to further examine variants of unknown significance (VUS).RESULTS:
In the 24 genes on the ACMG SF v2.0 list associated with a cancer phenotype, we observed 8 P/LP unique variants (8 individuals; 0.8%) in controls and 11 P/LP unique variants (14 individuals; 1.2%) in cases, a non-significant difference. We reviewed 115 VUS. The median estimated per-variant review time required was 30 min; the first variant within a gene took significantly (p = 0.0009) longer to review (median = 60 min) compared with subsequent variants (median = 30 min). The concordance rate was 83.3% for the variants examined by two reviewers.CONCLUSION:
The 115 VUS required database and literature review, a time- and labor-intensive process hampered by the difficulty in interpreting conflicting P/LP determinations. By rigorously investigating the 24 ACMG SF v2.0 cancer genes, our work establishes a benchmark P/LP variant prevalence rate in a familial cancer cohort and controls.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
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Genes Neoplásicos
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Mutação
/
Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
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Observational_studies
/
Prevalence_studies
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Risk_factors_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
Genome Med
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos